[Letter to Daniel K. Inouye from Anthony S. Fauci]

HIV VACCINE EFFICACY TRIALS. What are the numerical size and the demographics of the population that would be subjects of
an AIDS vaccine efficacy test? How did the ad hoc committee determine the population
needed for a study? How many trials could the available population support?
The size of the population for inclusion in vaccine efficacy studies would depend on a variety
of factors including the annual estimated rates of HIV transmission in the population being
studied (seroincidence rates), the estimated efficacy of the candidate vaccine, the length of
follow-up (years) for the duration of the efficacy trial, and the anticipated effects of effective
counseling on lowering seroincidence rates. In general, it is anticipated that efficacy trials
would be standard double-blind, placebo-controlled, with several hundreds to thousands of
volunteers depending on factors discussed above. The potential populations that would be the
subjects of HIV vaccine efficacy trials in the United States include: young homosexual males;
intravenous drug users; sexually transmitted disease clinic patients; spouses of hemophiliacs;
and HIV infected pregnant women for prevention of HIV to newborns. In addition, several
international populations have significant rates of HIV transmission, which might enablevaccine efficacy trials to be conducted at various global sites.
There have been several meetings with representatives from National Institutes of Health
(NIH), in collaboration with other Public Health Service agencies, and international programs
in HIV vaccine development (in particular, the W.H.O. Global Programme on AIDS) to
develop guidelines for vaccine efficacy trials and to begin the planning to insure that the best
candidate HIV vaccines progress expeditiously through efficacy trials. Given the potential
number of sites for HIV vaccine trials worldwide, and the diversity of the virus in differing
geographic locations, it is likely that multiple vaccine candidates will be entering into efficacy
trials in the next few years. The HIV seroincidence rate in various U.S. populations suggests
that 1-3 trials may be possible in the near future. This number is contingent on the ability to
rapidly identify cohorts from these populations that can be reliably followed.
2. Given that the epidemic is spreading to other groups (i.e., from homosexuals to intravenous
drug users to spouses of bisexuals and drug users to infants born of infected mothers to
college students), what would prevent subsequent tests from being run on groups which may
be at higher risk in the future? Is it possible that some populations which could be included
in efficacy tests within the next 12 months will become so infected that they could not be
included in future efficacy tests?
The dynamic state of HIV transmission worldwide is another factor that impacts on the choice
of sites/populations for vaccine efficacy trials. Thus, it is possible that some populations
identified as optimal in 1991 may not be optimal in 1995, due to both scientific (changing
rates of HIV transmission) and socio-political factors. The primary factors in choosing a
population for vaccine efficacy trials are that seroincidence rates of HIV infection are high
enough to evaluate if the vaccine is effective and that the populations are accessible and
compliant to long term follow-up during vaccine evaluations. For this reason, the NIAID will
establish infrastructures at several sites, so that an appropriate site and population can be
selected when a vaccine candidate is moved into efficacy trials.